This application is being made for renewal of USPHS grant AM 18061. The proposed study is a continuation of research activities directed towards understanding the mechanism controlling the adaptive change in renal function to increase the excretion rate of potassium following a rise in the excretory load of potassium, at the level of individual nephrons. This process occurs both in subjects with intact renal function after dietary load is increased and in chronic renal insufficiency in the absence of a change in dietary potassium. Specific goals include an elucidation of the cellular mechanism responsible for potassium secretion in different segments of the distal tubule and collecting duct, the relative importance of potassium secretion to urinary potassium in those segments, and the role of changes in surface area and composition of basolateral cell membrane on potassium movement in normal and potassium adapted animals. In addition, we plan to evaluate the mechanism by which sodium transport influences the rate of potassium secretion in distal nephron segments. These experiments will utilize micropuncture and microcatherization techniques, the determination of enzyme activity in epithelial cells and in cell fractions, morphometric techniques to estimate surface area of cell membrane and special techniques for determining the concentration of ammonia in small aliquots of tubular fluid. We hope that these studies will provide greater understanding of the cellular transport mechanism for potassium, the role of different nephron segments in modulating urinary potassium content and the factors which control or influence cellular transport.